Omega-3 unsaturated fatty acids

Description

Omega-3 unsaturated fatty acids are fatty acids with a double (i.e. unsaturated) bond in the third position. Three substances are most commonly classified here:

alpha-linoleic acid (ALA),

ecosapentaenoic acid (EPA),

docosahexaenoic acid (DHA).

However, omega-3 unsaturated fatty acids also include other substances, such as stearidonic acid (SA).

While the longer-chain omega-3 unsaturated fatty acids DHA and EPA are found in animal tissues, the shorter-chain omega-3s ALA and SA are found in plant sources. The only exception is seaweed, which, in addition to ALA and SA, also contains significant amounts of DHA and EPA. However, ALA can be converted to DHA and EPA to a limited extent in the human body. At the same time, EPA can be converted to DHA in the body (74, 76).

DHA is an important building block of cell membranes. It is particularly abundant in the membranes of nerve cells, especially in the cells of the frontal lobe of the cerebral cortex, where it accounts for 15% of all fatty acids. It is an essential substance for the transmission of nerve impulses, cell signalling and glucose metabolism in the cerebral cortex. Some metabolites of DHA even protect brain cells from the action of free radicals. The frontal lobe is the area responsible for cognitive processes such as learning, attention, planning and problem solving, and is also closely linked to the limbic system, which is closely related to emotions and therefore social development. Adequate intake of DHA is therefore essential, especially in pregnancy and in children under two years of age, and its deficiency can lead to severe cognitive problems (45-48).

EPA is also a component of cell membranes, but its most important function is to prevent inflammatory processes in the body (see below). Adequate intake is essential throughout life.

Yet research shows that the vast majority of the Western population is critically deficient in omega-3s, which can result in increased incidence of a number of diseases of civilization. The absolute minimum amount needed to maintain good health is considered to be 1750 mg of EPA and DHA per week, i.e. about 250 mg per day, but much higher amounts (1-4 g per day) are considered optimal. However, in a large survey of the US population, researchers found that only 27% of the population consumed at least the minimum recommended amount of 250 g per day. (11) No similar research has been conducted in the Czech Republic, but it can be assumed that the situation will be similar here.

Occurrence

ALA is abundant in vegetable oils such as rapeseed, sunflower and flaxseed, and is also found in seeds (e.g. pumpkin and sunflower seeds), sheep and goat milk and fish. The most important source of EPA and DHA is fish, specifically fish oil, but it is also found to a lesser extent in other foods of animal origin, especially eggs, and to a lesser extent in meat and dairy products. The only plant food containing EPA and DHA is seaweed.

Since ALA, which is abundant in many plant sources, can be converted into both EPA and DHA, it would seem that vegans should have no problem getting enough omega-3s. But the situation is more complicated. While herbivores can carry out this conversion in their bodies quite efficiently, in the human body no more than 9% of the ALA ingested is converted to EPA and DHA, of which about 8% is converted to EPA and 1% to DHA. In contrast to EPA and DHA, which are stored in cell membranes, ALA is not stored in the body and, because the body has only a limited metabolic capacity to convert it, the remainder is oxidised and used as an energy source (69).

The situation is further complicated if we also consume an excess of another type of unsaturated fatty acid – omega-6, especially linoleic acid. This not only promotes inflammatory processes in the body (see below), but also uses the same metabolic pathways as ALA (in particular the enzyme desaturase), reducing the efficiency of its conversion to EPA and DHA (69).

Therefore, given the limited ability to convert ALA to EPA, and especially to DHA, it is preferable to prefer animal sources of omega-3s (especially fish oil) at least at certain times of life. This is particularly important in childhood, when the body not only needs a high overall intake of omega-3s, but also, due to the development of the nervous system, a significantly higher proportion of DHA than in adulthood.

Stearidonic acid (SA) appears to be a slightly better plant source of omega-3. It too can be converted to EPA and DHA, but because it does not require the enzyme desaturase, this conversion is significantly more efficient than with ALA – for example, about twice as much EPA was found in the red blood cells of people taking SA as in those taking ALA. It should be noted, however, that most of the research on the benefits of consuming SA has been funded by an American company that has developed a genetically modified soybean oil enriched with SA. In contrast, SA is found only in small amounts in natural foods, with only hemp oil and seaweed being significant sources (71-73, 76).

History

The first comprehensive findings on the health effects of omega-3 unsaturated fatty acids were published in 1956. At that time, studies showed an association of their intake with cardiovascular health, specifically with the rate of atherosclerotic changes and the incidence of coronary heart disease and myocardial infarction (1, 2). Gradually, research mapping other beneficial effects has accumulated, and in the last 15 years, the epigenetic effects of omega-3s, i.e. the ability to influence the activity of important genes within human DNA, have been repeatedly demonstrated.

Effect on health

The mechanisms by which omega-3 unsaturated fatty acids affect human health are numerous. Among the most significant are the effects on the production of hormones that regulate cellular function, as well as epigenetic effects, which consist of turning certain genes on and off. Both EPA and DHA affect the process of methylation, which involves the binding of a methyl group to DNA, and it is this biochemical reaction that switches genes off. Research among Alaska Natives, who consume up to 20 times more fish than the general US population, has shown different methylation patterns in a total of 27 DNA regions, 78% of which have been shown to be associated with high omega-3 consumption. In addition, these were predominantly epigenetic changes associated with greater resistance to cardiovascular disease and inflammatory processes. The total number of genes exclusively influenced by EPA and DHA is around 900 (3-8).

Fetal development in pregnancy

Omega-3 fatty acids are essential for proper fetal development during pregnancy, especially for the brain development of the unborn child.

In a Japanese study in which mice were fed a diet low in these fatty acids, their offspring were shown to have smaller brains at birth, which not only affected their cognitive function in later life, but also caused different emotional behaviour, particularly a higher tendency to anxiety symptoms (13). According to the authors of the research, the cause is the premature ageing of so-called fetal neural stem cells, which give rise to brain cells during intrauterine development. Moreover, the problems persisted even when the young mice received sufficient omega-3 in their diet during their later life.

The close relationship between omega-3 consumption and brain development is also true in humans, as shown, for example, in a large study by Canadian scientists. Alarmingly, the researchers found that only a quarter of women consume enough of this nutrient during pregnancy and three months after giving birth (14).

Cognitive function

As mentioned in the introduction, DHA in particular is an important structural component of nerve cells, and its deficiency can therefore significantly impair cognitive function as well as emotional and social behaviour. This is most pronounced in children under two years of age, when brain structures are still undergoing intensive development (49). Thus, at this time, omega-3 deficiency can also negatively affect visual function. However, DHA intake later in life is also important – for example, five out of seven scientific studies have shown that DHA use leads to improved school performance in children, including learning, reading and spelling (48).

However, EPA is also important in childhood – for example, it has been shown to be deficient in children with ADHA (attention deficit hyperactivity disorder). Omega-3s (both EPA and DHA) can also be used in the treatment of children with ADHD, but relatively high doses (1-2 g of omega-3s per day) have been shown to be necessary to achieve improvement (50). The presence of EPA is particularly important here because children with ADHD have higher rates of inflammatory processes in their bodies – indeed, it is not without interest that they are also more likely to suffer from allergies and asthma compared to the general child population (51, 52).

However, sufficient EPA and DHA consumption has also been shown to have a beneficial effect on slowing cognitive decline and memory loss with age (11). In addition, high blood levels of omega-3s can significantly reduce the incidence of cerebral infarcts and small lesions in the elderly by up to 40%. These brain abnormalities occur in about 20% of people over 65 years of age and significantly increase the risk of cognitive and memory decline, as well as the risk of dementia and stroke (15).

Another study showed that older people with low blood levels of omega-3s have smaller brain volume (a difference equivalent to the effect of about two years of ageing) and experience faster decline in memory and other cognitive abilities, such as problem-solving and analytical thinking (16). Regardless of age, people who consume fish at least once a week have a greater volume of grey matter in the brain regions responsible for memory (by 4.3%) and cognitive function (by as much as 14%) compared to others (18).

In addition, some studies have also suggested an effect of sufficient omega-3 consumption on the risk of developing Alzheimer’s disease. For example, increasing their consumption by 1 g per week led to a 20-30% reduction in blood beta-amyloid levels in people over 65 years of age (17). Elevated blood levels of beta-amyloids can lead to the formation of beta-amyloid plaques in the brain, which are a characteristic manifestation of Alzheimer’s disease. People who eat fish at least once a week also have a higher overall brain grey matter volume, which also significantly reduces the risk of developing Alzheimer’s disease (19). A positive effect of omega-3 consumption has been observed particularly in the area of working memory, which tends to be particularly severely affected in patients. A functioning working memory is essential for solving any task.

Adequate consumption of EPA is important in Alzheimer’s disease because inflammatory processes contribute greatly to the degradation of nerve cells. At the same time, however, significantly reduced levels of DHA have also been observed in sufferers, so it is important to ensure the intake of this unsaturated acid (69).

Inflammatory processes

A key role of omega-3 unsaturated fatty acids is to positively influence the rate of inflammatory processes in the body. This is fundamentally important because inflammation is a mechanism that is involved in the development of many diseases, including the most serious ones. There are a number of mechanisms by which omega-3s influence the rate of inflammatory processes, but in principle, consuming enough of them is one of the most important factors that can help us fight inflammation.

EPA, DHA and ALA are all very powerful natural inhibitors of the enzyme cyclooxygenase 2 (COX-2), a substance that triggers the production of prostaglandins, substances that cause inflammation and pain. In addition, unlike anti-inflammatory drugs in the category of non-steroidal anti-inflammatory drugs, it acts selectively only on COX-2 and not on COX-1, which is essential, for example, for maintaining the integrity of the gastric mucosa or for regulating blood flow through the kidneys. As a result, omega-3s are able to relieve pain and inflammation without the side effects typical of NSAIDs – in particular, a wide range of gastric problems, from feelings of heaviness and indigestion to ulcer disease and severe, life-threatening bleeding conditions (9, 18).

Both EPA and DHA are part of cell membranes – they not only perform a number of important functions, but also serve as a reservoir of cell membranes. However, the exact amount of omega-3s in them is greatly influenced by our diet. People who eat a “typical Western diet”, which is rich in omega-6 unsaturated fatty acids and poor in omega-3s, have low levels of both EPA and DHA in their cell membranes, but high levels of arachidonic acid. However, it is from arachidonic acid (which also uses similar enzymatic pathways) that prostaglandins, substances with a direct inflammatory effect, are synthesised in the body. It is therefore important not only to increase the intake of omega-3s in the diet, but also to reduce the consumption of omega-6 unsaturated acids as much as possible. These are abundant in many vegetable oils, such as soybean, corn and sunflower oils.

However, omega-3s also positively influence inflammatory processes through a number of other mechanisms, many of which have not yet been studied in detail – for example, they affect cell signalling (i.e. the ability of a cell to receive information from its environment and regulate its functions on the basis of this information), the synthesis of certain hormones, have a direct effect on the function of certain immune cells (e.g. leukocytes) or the production of inflammatory cytokines, etc. (59)

Cardiovascular disease

But probably the most well-known area of beneficial effects of omega-3 unsaturated fatty acids is the prevention of cardiovascular disease. There are several mechanisms by which they act in this regard, but their epigenetic action also plays an important role. They can turn off genes responsible for inflammatory processes in the vascular lining and the formation of atherosclerotic plaques (24). Epigenetic changes that increase the disposition to cardiovascular disease have been shown to occur in early childhood and even during intrauterine development (25). Adequate intake of omega-3s is therefore important for heart health not only in adulthood but also in early childhood.

In addition, omega-3s reduce blood triglyceride and LDL cholesterol levels, blood pressure, atherosclerotic plaque formation, and the risk of cardiac arrhythmias and venous thrombosis (29,30).

Autoimmune diseases

The combination of potent anti-inflammatory and epigenetic effects of omega-3s plays a very important role in the prevention and treatment of virtually all autoimmune diseases (60).

They can be especially useful for people suffering from rheumatoid arthritis. In addition to pain and inflammation, degradation of the articular cartilage is a characteristic feature of this disease. This is due to the production of the enzyme aggrecanase, which breaks down a protein called aggrecan. This is abundant in articular cartilage and significantly increases its elasticity. Omega-3s can significantly reduce the activity of aggrecanase. (20, 21)

Benefit has also been demonstrated for Bechterew’s disease. In studies, higher doses of omega-3 (above 4.5 g/day) have been shown to significantly reduce the BASDAI index, which measures disease activity, in people with the disease (61).

Patients with inflammatory bowel diseases of autoimmune origin, in particular Crohn’s disease and ulcerative colitis, are also very often deficient in these substances. In addition, the mucosa of the digestive tract is very sensitive to omega-3 concentrations, as these substances suppress the production of inflammatory cytokines and nuclear factor NF-kB. In addition, two of these acids, ALA and DHA, have been shown to reduce the pain that accompanies inflammatory bowel disease (62, 63).

Mental illness

Omega-3 deficiency has been linked to many mental illnesses, especially depression and anxiety.

However, Australian scientists from the Menzies Research Institute in Tasmania have come up with an interesting finding in this area. In a large-scale study involving more than 1,400 volunteers, they found that adding omega-3s to the diet can reduce the risk of depression by 25%. Interestingly, however, this effect has only been shown in women. The exact reason for this is unknown to the authors of the research – it may be that most men consume more omega-3s in their diet, but the interaction of these fatty acids with female sex hormones may also play a role (10).

In depression, EPA is more effective than DHA, probably due to the fact that the brain undergoes inflammatory processes (58).

Consequences of smoking

Research also shows that sufficient consumption of omega-3s can reduce the negative health effects of smoking. This is particularly true in the area of cardiovascular health, where the negative effects of smoking on vascular health in particular are reduced by reducing the incidence of inflammatory and sclerotic processes in blood vessels and increasing the elasticity of blood vessel walls (12).

Omega-3 supplementation (specifically DHA) is very important for pregnant smokers, whose unborn children are much more likely to suffer from methylation pattern disorders compared to children of non-smokers. In this case, the use of DHA will help to stabilise important genes, improve the immune function of the children and reduce the incidence of allergies throughout life (31).

Tumour diseases

The epigenetic action of omega-3s is also beneficial in the prevention and treatment of cancer. Through methylation, they are able to shut down important genes inside cancer cells, thereby stopping them from multiplying and causing cell death. So far, this effect has been demonstrated in breast and prostate cancer (22, 23).

Obesity

Omega-3s can also help obese people lose weight. The hormone leptin, which is produced by adipose tissue and regulates feelings of satiety, plays an important role in this. It essentially tells the brain that there is enough fat and therefore increased food consumption is not needed. However, in people in the obese stage, there is what is known as leptin resistance: High amounts of adipose tissue produce leptin in excess, so the body loses sensitivity to it, the feeling of satiety does not occur, and this leads to overeating. Leptin resistance is therefore one of the reasons why obese people overeat so much. In fact, this creates a vicious circle – overeating increases the volume of adipose tissue and therefore the production of leptin, which in turn increases leptin resistance and with it the appetite (26, 27).

Omega-3, through epigenetic mechanisms, influences leptin production and, in addition, has a positive effect on other processes related to the development of obesity, especially on adipogenesis, i.e. the proliferation of fat cells and their differentiation (28).

Thyroid gland

Omega-3s enhance iodide uptake, an important mechanism to ensure that the thyroid gland has enough iodine for hormone production. They also increase the number of receptors to which thyroid hormones bind in individual cells. They also prevent cognitive decline due to thyroid dysfunction. The anti-inflammatory effect is then applied to thyroid hyperfunction and autoimmune disorders in this organ (67, 68).

Immunity

Omega-3s are very effective immunomodulators. They improve the transmission of signals between immune cells and thus improve their ability to destroy pathogens. They also support the function of lysosomes, which are organelles essential for cellular defence and cellular immunity. Anti-inflammatory action is also important, as increased levels of inflammation in the body generally lead to a reduction in immune cell activity. This is particularly effective in the elderly, where the use of omega-3s not only improves the immune system’s ability to fight pathogens but also reduces the risk of autoimmune disease (32).

Asthma and allergies

Taking omega-3s can be very effective for asthma and allergies. For example, in a 10-month study, asthma symptoms improved significantly in children taking as little as 120 mg of a mixture of EPA and DHA per day (53).

Sleep disorders

Omega-3s are also effective for sleep problems, and this is already true for children. In a study involving nearly four hundred children with low levels of these unsaturated fatty acids, for example, after 16 weeks of taking 600 mg of DHA daily, the children studied experienced a decrease in the frequency of night wakings and an increase in total sleep time of about one hour (54). Omega-3 use in pregnancy has even been shown to lead to better sleep habits in newborns (55).

Taking omega-3s can also help with many adult sleep disorders, but this cannot be said to be general – it depends on the specific cause of the problem. For example, the results of a study looking at the prevalence of sleep apnoea, which is essentially a brief cessation of breathing during sleep that significantly impairs sleep quality, causes high levels of fatigue and an increased risk of certain health problems (people with severe sleep apnoea have up to 3 times the risk of death), are interesting. Low levels of DHA have been shown to significantly increase the incidence and severity of sleep apnoea. At the same time, people with sleep apnoea have a significantly higher rate of inflammatory processes in the body, so it is important to take EPA in addition to DHA (56, 57).

Eye health

EPA and DHA are also abundant in the membranes of nerve cells that make up the retina and optic nerve. Adequate intake is also important for the prevention of eye defects and cataracts caused by ageing. In fact, low levels of omega-3 have been found in people with this disease. DHA also produces neuroprotectin D1, a substance with a strong protective effect on nerve cells, and is also important for maintaining optimal permeability and thickness of the cell membranes of rods and cones and for activating specific proteins in the retina. (64-66)

Sports performance

Taking omega-3 is also very useful for athletes across disciplines as it will help boost performance and speed recovery after exercise. Strength athletes can benefit from them, as in combination with strength training and sufficient protein intake, they promote muscle growth (the so-called anabolic effect) and increase strength. They increase the insulin-sensitive aspects of protein metabolism (33-35).

For strength, speed and endurance athletes, the anti-inflammatory action of omega-3 is important. During strenuous physical activity, microscopic damage to muscle fibres occurs, to which the body reacts with inflammation and muscle pain. Omega-3s reduce inflammation and pain while accelerating muscle repair. This speeds up the recovery process so that the athlete can undergo further demanding training leading to increased performance sooner (36, 37).

Omega-3s also mitigate the decline in immune function that typically occurs after strenuous physical activity (38).

Endurance athletes in particular can benefit from the beneficial effect of omega-3s on cardiovascular function, which results in the heart being able to deliver more oxygen to working muscles. The use of omega-3s in conjunction with endurance training has also been shown to improve lung function even more than training alone. VO2max (maximal oxygen consumption), one of the main indicators of aerobic endurance, is also improved (39-42).

Use of

In the Czech Republic, omega-3s are approved as a dietary supplement, but in some countries (Austria, USA) they are even used as a therapeutic agent, especially in the case of dyslipidemia disorders (i.e. for example to lower cholesterol levels). The recommended daily dose in this case is 1-4 g. There is even a product specifically developed for use at the same time as statins, which are the most commonly prescribed cholesterol-lowering drugs. Daily doses of 250 mg- 1 g are used for prevention (43).

In addition, the ratio of omega-3 to omega-6 unsaturated fatty acids, which are much more common in the diet, is important for the body. The ratio should be between 1:1 and 1:4 (in favour of omega-6), but in most of our diets it is up to ten times higher (44).

The optimal ratio of EPA and DHA intake is also an important issue. In general, children, especially young children, should take more DHA than EPA. In fact, even breast milk contains significantly more DHA than EPA – usually stated to be 4 times more, but specific values can vary considerably. In fact, the content of DHA (and EPA) in breast milk varies considerably depending on the mother’s diet. For example, studies have reported DHA concentrations in breast milk ranging from 0.06 to 1.4 percent by weight, a difference of more than 20 times! (69, 75)

However, the exception is children with ADHD, where EPA is important for more effective reduction of inflammatory processes. There it is advisable to increase EPA intake significantly, and the same applies to children suffering from any inflammatory diseases. In adulthood, on the other hand, it is preferable to take a slightly higher proportion of EPA relative to DHA, but there are exceptions. For example, in Alzheimer’s disease and other neurodegenerative diseases, while EPA is important because it helps to suppress inflammatory processes that promote nerve cell destruction, it is also true that in most cases, sufferers have low concentrations of DHA in their bodies (69).

Specifically for Alzheimer’s disease, for example, good results have been achieved with a daily intake of 1.7 g of DHA and 0.6 g of EPA. Higher levels of DHA may also be preferable for pregnant women, for whom 200 mg of DHA per day is recommended as a minimum daily dose (74).

In principle, however, even people with higher DHA intake requirements can safely use sources with a higher proportion of EPA, as this fatty acid can be converted to DHA in the body.

Taking ALA as a dietary supplement is not effective. Vegans and vegetarians can opt for seaweed oil, which often has a very high DHA content, making it more suitable for children (but depending on the type of seaweed used, the differences can be really significant), or dietary supplements with stearidonic acid.